1. Field of the Invention
The present invention relates to novel guanidine derivatives or salts thereof, a process for production thereof, and pharmaceutical uses thereof. The compounds of the present invention have inhibitory effect on the sodium/proton (Na.sup.+ /H.sup.+) exchange transport system and hence are useful as a therapeutic or prophylactic agent for diseases caused by the acceleration of the sodium/proton (Na.sup.+ /H.sup.+) exchange transport system, for example, hyperpiesia, arrhythmia, angina pectoris, hypercardia, diabetes, organopathies due to ischemia or ischemia re-perfusion [for instance, troubles caused by myocardial ischemia re-perfusion, acute renal failute, and surgical treatments (e.g. organ transplantation and PTCA (percutaneous transluminal coronary angioplasty))], troubles due to cerebral ischemia (e.g. troubles accompanying cerebral infarction, troubles brought about as after-effects of cerebral apoplexy, and cerebral edema), diseases caused by cell over-proliferations (e.g. fibroblast proliferation, smooth muscle cell proliferation and mesangial cell proliferation) (e.g. atherosclerosis, fibroid lung, fibroid liver, fibroid kidney, renal glomerulosclerosis, organ hypertrophy, prostatomegaly, complications of diabetes, and re-constriction after PTCA), and diseases caused by trouble with endothelial cells.
2. Related Art Statement
As substituted guanidine derivatives having inhibitory effect on the sodium/proton Na.sup.+ /H.sup.+) exchange transport system, there are known, for example, pyrazinoylguanidine derivatives represented by amiloride (for instance, J. Membrane Biol., Vol. 105, 1 (1988); Circulation, Vol. 79, 1257 (1989)). It has been reported that benzoylguanidine derivatives have inhibitory effect on the sodium/proton Na.sup.+ /H.sup.+) exchange transport system and hence antiarrhythmic effect (for instance, J. Mol. Cell. Cardiol., Vol. 24, Suppl. I, S. 92 (1992); J. Mol. Cell. Cardiol., Vol. 24, Suppl. I, S. 117 (1992), Japanese Patent Unexamined Publication Nos. 5-339228, 6-9545, 6-345715 and 7-109251). It has also been reported that polycyclic aroylguanidine derivatives have inhibitory effect on the sodium/proton Na+/H+) exchange transport system (for instance, Japanese Patent Unexamined Publication Nos. 7-10839, 7-145149 and 7-206823).